Kidney disease is a frequent complication of monoclonal gammopathies and multiple myeloma, and it manifests with a wide range of renal lesions. The nonmalignant nature of clonal disorders had been a source of confusion for clinicians with regard to the need for treatment, and the term monoclonal gammopathy of renal significance was introduced by the International Kidney and Monoclonal Gammopathy Research Group in 2012. 

A patient with MGUS, by definition, does not meet the criteria for multiple myeloma, as there are no CRAB symptoms (ie, hypercalcemia, renal failure, anemia, and lytic bone lesions) and the plasma cell percentage in the bone marrow is under 10%. However, the significance is not undetermined if that patient has impending or current renal damage; rather, there is renal significance (ie, MGRS).  

M proteins that are secreted by a clone can be directly nephrotoxic and also indirectly nephrotoxic by complement activation. M proteins may also have autoantibody activity that causes complement activation. The type of kidney injury seems to be related to the characteristics of the M protein, and the lesions can have glomerular, tubulointerstitial, and vascular patterns of injury, alone or in combination. Patients with MGRS may have a high morbidity due to the severity of renal and, possibly, systemic lesions that are induced by the M protein. One classic example of MGRS is amyloidosis, but a number of kidney diseases are associated with monoclonal gammopathy, and the list of recognized entities is still expanding.

Further, MGRS may complicate a previously diagnosed clonal B-cell disorder, or it may be the initial manifestation of the hematological disease. MGRS was only recently recognized as a treatable condition, for which the treatment is directed toward the underlying clonal disorder, just as the treatment for multiple myeloma is directed toward the malignant plasma cells. For optimal care, it is recommended that patients be treated by a multidisciplinary team consisting of nephrologists, hematologists, and nephropathologists with expertise in MGRS.

Johnson et al described a case involving a 64-year-old man with dyspnea, elevated serum creatinine (4.6 mg/dL), hematuria (3+), and proteinuria (3.7 g/24 h). The patient had developed MGRS with dominant glomerular C3G. The authors found that his monoclonal immunoglobulin G kappa directly bound to the N terminus of factor H, which functioned as a blocking autoantibody and interfered with this natural complement-dampening mechanism. In other situations, one might have a paraprotein that is a C3 nephritic factor, and this, of course, would also unleash the alternative complement pathway to cause C3G. 

While this case is interesting, the cause of the renal pathology of C3G would only very rarely be a paraprotein from MGRS. C3G typically presents in childhood, and it is very uncommon to develop C3G after age 50 years. Further, in most cases, the cause is unknown. Still, this case does highlight that we should be thinking about MGUS and MGRS. The key message is that M protein screening should be considered in patients with unexplained proteinuria or renal dysfunction, especially in those who are over 50 years of age.